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Isolation and Characterization of Adult Cardiac Fibroblasts and Myofibroblasts
Published on: March 12, 2020
Structural and functional changes in heparan sulfate proteoglycan expression associated with the myofibroblastic
Gareth Thomas1, Aled Clayton, Janet Thomas
1Institute of Nephrology, University of Wales College of Medicine, Heath Park, Cardiff, Wales, UK.
The American Journal of Pathology
|February 25, 2003
Summary
Myofibroblasts, key in fibrosis, show altered heparan sulfate (HS) proteoglycans, impairing fibroblast growth factor-2 (FGF-2) response. This difference in HS structure affects FGF-2 binding and cell proliferation.
Area of Science:
- Cell Biology
- Biochemistry
- Extracellular Matrix Research
Background:
- Fibrosis involves myofibroblasts producing extracellular matrix.
- Myofibroblasts exhibit altered heparan sulfate proteoglycan (HSPG) expression compared to normal fibroblasts.
- These alterations are linked to impaired responses to fibroblast growth factor-2 (FGF-2).
Purpose of the Study:
- To investigate the differences in heparan sulfate (HS) proteoglycan expression between myofibroblasts and normal fibroblasts.
- To understand the impact of these differences on fibroblast growth factor-2 (FGF-2) responsiveness.
- To elucidate the structural basis for altered FGF-2 signaling in fibrotic cells.
Main Methods:
- Comparative analysis of HSPG expression in myofibroblasts and fibroblasts.
- Cell proliferation assays using FGF-2, platelet-derived growth factor, HS, and heparin.
- Biochemical analysis of HS-glycosaminoglycan chains, including selective digestion and size/composition determination.
- Measurement of FGF-2 binding affinity and capacity to HS chains.
Main Results:
- Myofibroblasts, unlike fibroblasts, did not proliferate in response to FGF-2 alone but did when HS or heparin was present.
- HS-glycosaminoglycan chains from myofibroblasts were larger and had more heparinase 1-resistant sequences than those from fibroblasts.
- Myofibroblast HS chains exhibited twice the binding capacity for FGF-2 compared to fibroblast HS chains, despite similar binding affinity.
Conclusions:
- Differences in HS fine structure and composition in myofibroblasts likely account for their impaired response to FGF-2.
- Altered FGF-2 sequestration and receptor interaction due to modified HS complexes are implicated in fibrotic processes.
- Further investigation into HS fine structure is warranted to fully understand these mechanisms in fibrosis.
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